Volume Articles

The Clinicoanatomic Uniqueness of the Human Pyramidal Tract and Syndrome

Ricardo de Oliveira-Souza

The chief goal of the present review is to present clinicoanatomic evidence that, (i) in contrast to most vertebrates, spastic hemiplegia in man is a symptom of damage to the pyramidal tracts, and (ii) although extrapyramidal structures are often injured as a contingency of anatomical proximity in cases of pyramidal damage, the extrapyramidal system plays no role in the production of human spastic hemiplegia. The views herein discussed reconcile several apparent incongruences concerning the pathophysiology of the human pyramidal syndrome. From a neurobiological perspective, the progressive commitment to occasional, habitual and obligate bipedalism fostered a profound internal reorganization of the mammalian brain at the early stages of human phylogenesis. The major anatomical counterpart of this reorganization was an unprecedented increase of the ansa lenticularis fiber system, which ultimately redirected the product of subcortical motor activity up to the motor cortices from which the pyramidal tracts originate. In this sense, while the fundamental motor organization of vertebrates is represented by the extrapyramidal system, the dominant motor plan in humans is uniquely represented by the prepyramidal system.

Heterozygous eNOS Deficient Mice as a Model to Examine the Effects of eNOS Haploinsufficiency on the Cerebral Circulation

Sean P. Didion, PhD¹

Nitric oxide derived from endothelial nitric oxide synthase (eNOS) has been shown to be a major mediator of endothelium-dependent responses in cerebral blood vessels. Loss of a single eNOS gene is not associated with any apparent negative consequences on endothelial function in most blood vessels. In contrast, we have recently demonstrated that heterozygous eNOS gene deficiency in combination with a high fat diet is associated with marked impairment of endothelial function. These findings provide an important example of eNOS haploinsufficiency and one that directly impacts the cerebral vasculature. A major mechanism associated with the impairment of endothelial function with eNOS deficiency and a high fat diet appears to be related to increases in plasma IL-6 that serves to further reduce the bioavailability of NO either directly or indirectly via reductions in eNOS expression or activity and via increases in vascular superoxide. Taken together, these findings provide important insights into genetic and molecular mechanisms that promote endothelial dysfunction in response to a high fat diet in cerebral blood vessels with inherent reductions in eNOS gene expression, such as those due to eNOS gene polymorphisms. These findings also highlight the importance of eNOS+/- mice to study the effects of eNOS haploinsufficiency on cerebral blood vessels.

Karenitecin (BNP1350) radiosensitizes glioma cells with an associated increase in caspase activation and reactive oxygen species.

Deepika Rajesh, H. Ian Robins* and Steven. P. Howard

The prognosis for patients with high-grade glioma remains dismal illustrating the need for the development of chemotherapeutic strategies intended to synergize with treatment modalities of proven efficacy such as radiation therapy. Karenitecin, (BNP1350,7-[(2-trimethylsilyl)ethyl]-20(S)-camptothecin), is a semisynthetic, orally administrable camptothecin, with physiochemical properties favoring increased accumulation of active drug within the central nervous system. This study was initiated to determine whether Karenitecin could potentiate radiosensitivity in T98G and MO59K glioma cell lines. Using clinically relevant doses of each agent, it was demonstrated that Karenitecin pretreatment significantly enhances radiosensitivity and was shown to be synergistic by isobolographic analysis. Karenitecin treatment resulted in a transient arrest in the G2/M phase of the cell cycle with an associated increase in expression of cyclin B1. It was further demonstrated that Karenitecin treatment results in activation of caspases, generation of reactive oxygen species, collapse of the mitochondrial membrane potential and inhibition of total protein kinase C, all of which could enhance radiosensitivity. These in vitro data suggest that Karenitecin has potential as a radiosensitizer in the treatment of malignant glioma.

In-hospital stroke

Kolja Schürmann and Arno Reich

In-hospital stroke (IHS), which represents between 2.2% and 17% of all strokes, differs from community-onset stroke (COS) in etiology, treatment approaches and outcome. Patients hospitalized for cardiac disease are especially vulnerable to predominantly cardioembolic IHS. Stroke severity, functional outcome and mortality compare unfavorably to COS. Difficulties in symptom recognition, intra-hospital delays, various stroke mimics, critical underlying diseases and contraindications against standard systemic thrombolysis represent difficulties in IHS treatment. Quality of care may be improved by educating medical staff, implementing a code stroke and a CT-rendezvous system, providing access to specialized care (e.g. on stroke units) and endovascular reperfusion therapy as well as neuromonitoring, where applicable.

Fiberoptic Endoscopic Evaluation of Swallowing as possible index of ALS clinical development

Bruno Fattori¹, Gabriele Siciliano², Amelia Santoro¹, Salvatore Osvaldo Romeo¹, Andrea Nacci¹

Our purpose was to assess the relationship between the disease severity of Amyotrophic Lateral Sclerosis (ALS) and the main parameters of Fiberoptic Endoscopic Evaluation of Swallowing (FEES), indirectly hypothesizing for FEES a role as clinical indicator of the progression of ALS. We studied 220 patients (101 women, 119 men) with ALS; of these, 148 had spinal and 72 bulbar onset. They were analyzed according to the Amyotrophic Lateral Sclerosis Functioning Rating Scale (ALSFRS) and the b-ALSFRS subscale (bulbar scale). All subjects underwent FEES. Post-swallowing residue was classified into four classes (0-3); premature spillage and aspiration were considered either present or absent. An in-depth statistical analysis revealed a highly significant relationship between the FEES parameters studied and the severity of the disease assessed through ALSFRS and b-ALSFRS (p < 0.0001), no matter what bolus texture was used. Moreover, statistical analysis showed a highly significant association between the classes of severity in bulbar forms and all the FEES parameters, no matter what type of bolus was administered (p <0.0001), whereas a significant correlation in spinal forms only for post-swallowing residue with solid (p= 0.025) and semisolid (p= 0.034) boluses. FEES is a good indicator of the severity of dysphagia and of its progression in patients with ALS, as well as of the clinical progression of the disease. 

The time dimension of neurodegeneration: the example of Friedreich's ataxia

Tommaso Vannocci¹, Annalisa Pastore^1,2

¹Maurice Wohl Institute, King’s College London, 5 Cutcombe Rd., London SE5 9RT, UK
²Molecular Medicine Department, University of Pavia, Pavia, Italy